Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death

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Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death.

Excitotoxic cell death is the fundamental process responsible for many human neurodegenerative disorders, yet the basic mechanisms involved are not fully understood. Here, we exploited the fact that the immature brain is remarkably resistant to seizure-induced excitotoxic cell death and examined the underlying protective mechanisms. We found that, unlike in the adult, seizures do not increase t...

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Glutamate is the dominant excitatory neurotransmitter in the brain, but under conditions of metabolic stress it can accumulate to excitotoxic levels. Although pharmacologic modulation of excitatory amino acid receptors is well studied, minimal consideration has been given to targeting mitochondrial glutamate metabolism to control neurotransmitter levels. Here we demonstrate that chemical inhibi...

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Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes.

Uncoupling proteins (UCPs) are located in the mitochondrial inner membrane and partially dissipate the transmembrane proton electrochemical gradient. UCP2 is expressed in various human and rodent tissues, including the heart, where its functional role is unknown. In the present study, we tested the hypothesis that UCP2 overexpression could protect cardiomyocytes from oxidative stress-induced ce...

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Barbiturates induce mitochondrial depolarization and potentiate excitotoxic neuronal death.

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Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation

BACKGROUND/PURPOSE Major psychiatric illnesses, affecting 36% of the world's population, are profound disorders of thought, mood and behavior associated with underlying impairments in synaptic plasticity and cellular resilience. Mitochondria support energy demanding processes like neural transmission and synaptogenesis and are thus points of broadening interest in the energetics underlying the ...

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ژورنال

عنوان ژورنال: Annals of Neurology

سال: 2003

ISSN: 0364-5134

DOI: 10.1002/ana.10543